6-37453288-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015050.3(CMTR1):ā€‹c.753C>Gā€‹(p.Phe251Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

CMTR1
NM_015050.3 missense

Scores

5
5
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.92
Variant links:
Genes affected
CMTR1 (HGNC:21077): (cap methyltransferase 1) Enables mRNA (nucleoside-2'-O-)-methyltransferase activity. Involved in 7-methylguanosine mRNA capping and cap1 mRNA methylation. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CMTR1NM_015050.3 linkuse as main transcriptc.753C>G p.Phe251Leu missense_variant 8/24 ENST00000373451.9 NP_055865.1
CMTR1XM_047418462.1 linkuse as main transcriptc.753C>G p.Phe251Leu missense_variant 9/25 XP_047274418.1
CMTR1XM_047418463.1 linkuse as main transcriptc.753C>G p.Phe251Leu missense_variant 10/26 XP_047274419.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CMTR1ENST00000373451.9 linkuse as main transcriptc.753C>G p.Phe251Leu missense_variant 8/241 NM_015050.3 ENSP00000362550 P1
CMTR1ENST00000455891.5 linkuse as main transcriptc.609+1411C>G intron_variant 2 ENSP00000414233

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251420
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135878
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461868
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 26, 2022The c.753C>G (p.F251L) alteration is located in exon 8 (coding exon 7) of the CMTR1 gene. This alteration results from a C to G substitution at nucleotide position 753, causing the phenylalanine (F) at amino acid position 251 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.95
BayesDel_addAF
Pathogenic
0.27
D
BayesDel_noAF
Pathogenic
0.25
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.22
T
Eigen
Benign
-0.18
Eigen_PC
Benign
-0.065
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.93
D
M_CAP
Benign
0.020
T
MetaRNN
Uncertain
0.59
D
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.6
L
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.80
T
PROVEAN
Pathogenic
-5.4
D
REVEL
Uncertain
0.55
Sift
Benign
0.068
T
Sift4G
Benign
0.072
T
Polyphen
0.37
B
Vest4
0.88
MutPred
0.28
Loss of sheet (P = 0.1158);
MVP
0.84
MPC
2.1
ClinPred
0.97
D
GERP RS
2.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.84
gMVP
0.90

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs780906984; hg19: chr6-37421064; API